Potassium channels catalyze the movement of K+ ions across the cell membrane, and their function is essential for cellular electrical activity and electrolyte homeostasis. Many K+ channels are regulated by accessory-subunit proteins, which can be required for normal physiologic function and allow for the channels to adapt to changes of environmental conditions. This application describes the study of the beta subunit MiRP3, a novel member of the MinK-related peptide superfamily, which can modulate the properties of such K+ channels. I present preliminary evidence that suggests a role for MiRP3 in modulating cardiac electrophysiology, smooth-muscle function, and renal potassium secretion. Herein, I propose an extension of research project (K08 DK068188) that will utilize animal models to test these putative physiologic roles for MiRP3. I propose to use animal models to evaluate the physiologic role of the MiRP3 protein in the processes of cardiac electrophysiology, smooth-muscle function, and renal potassium secretion.